Otitis media is a term used to describe infections of the middle ear, which infections are very common, particularly in children. In children, the disease is most often associated with upper respiratory afflictions which trigger a transudate secretion response in the Eustachian tube and middle ear. Because of the immature anatomy of the child's skull (usually through about the age of 9), bacteria and viruses easily migrate from the naso-pharynx to the middle ear via the Eustachian tube. These events can cause the Eustachian tube to become blocked, preventing ventilation (pressure equilibration) and drainage of the middle ear.
In its more severe forms, where purulent exudate is formed in the middle ear, toxins and an abundance of endogenous anti-microbial enzymes can cause irreparable damage to sensory-neural and sound conducting structures. Recent research even suggests that many of the middle and inner ear diseases that are seen in adult patients can be attributed to a frequent and severe incidence of otitis in childhood. For this reason physicians are increasingly using antibiotics and ventilation devices prophylactically. It is estimated that over 1 billion dollars are spent annually in the United States on the treatment and prevention of otitis media. It has also been estimated that nearly 95% of all children experience one or more episodes of otitis by age 9, and that about 15% of all visits by children to pediatricians are in regard to otitis media.
Current methods of treatment generally involve the systemic use of antibiotics; the use of antibiotic-containing ear drops; and/or, particularly in more chronic cases, the insertion of a myringotomy tube through a small incision in the eardrum, in order to provide ventilation and allow drainage of the middle ear cavity over an extended period of time.
Myringotomy tubes however carry associated risks, e.g., of becoming plugged, falling out, or themselves providing an additional route for infection of the middle ear.
The effectiveness of antibiotic therapy for the middle ear is hampered by the routes of administration currently available. Typically antibiotics are systemically administered for infections of the middle ear, e.g., in a responsive or prophylactic manner. Systemic administration of antibiotics to combat middle ear infection generally results in a prolonged lag time to achieve therapeutic levels in the middle ear, and requires high initial doses in order to achieve such levels. These drawbacks complicate the ability to obtain therapeutic levels and may preclude the use of some antibiotics altogether. Systemic administration is most often effective when the infection has reached advanced stages, but at this point permanent damage may already have been done to the middle and inner ear structure.
Drugs also can be administered by injection or lavage to the middle ear, but such administration cannot generally be used to achieve prolonged therapeutic levels of antibiotic. Similarly ear drops can be used to apply antibiotics to the ear canal, but the ability of antibiotics to reach the middle ear when applied in this manner is difficult to predict or control, and carries questions, e.g., regarding the possible ototoxic effects of penetration enhancers that may be used. Middle ear drug delivery is further complicated by the fact that the ciliary action of the cells lining the mucous membrane has the effect of clearing the middle ear of medications that do arrive.
In one approach, German Patent No. DE 3,617,400 describes a method of injecting aerosol into the middle ear via the Eustachian tube. The aerosol is administered at the moment the patient swallows, which causes the Eustachian tube to open. Also U.S. Pat. Nos. 4,367,741 and 4,455,144 describe flexible walled dispensers which can be used to administer drug into a number of body cavities, including ear and ocular applications.
Clearly what is needed is a means to deliver therapeutically effective levels of drug to sufferers of chronic and recurrent otitis, and other diseases of the middle and/or inner ear, in a fashion that is prompt, responsive, prolonged, effective, and safe.